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CA3000063A1 - Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors - Google Patents

Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors Download PDF

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Publication number
CA3000063A1
CA3000063A1 CA3000063A CA3000063A CA3000063A1 CA 3000063 A1 CA3000063 A1 CA 3000063A1 CA 3000063 A CA3000063 A CA 3000063A CA 3000063 A CA3000063 A CA 3000063A CA 3000063 A1 CA3000063 A1 CA 3000063A1
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Prior art keywords
6alkyl
chiral
independently
intermediates
hydrogen
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CA3000063A
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English (en)
French (fr)
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CA3000063C (en
Inventor
Andreas Gollner
Joachim BROEKER
Nina Kerres
Christiane Kofink
Juergen Ramharter
Harald WEINSTABL
Annika GILLE
Stefan Goepper
Manuel Henry
Guenther Huchler
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Boehringer Ingelheim International GmbH
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Boehringer Ingelheim International GmbH
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/22Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • A61K31/41621,2-Diazoles condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/438The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
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    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • AHUMAN NECESSITIES
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    • A61P35/00Antineoplastic agents
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    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
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    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/22Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CA3000063A 2015-10-09 2016-10-07 Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors Active CA3000063C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15189210.6 2015-10-09
EP15189210 2015-10-09
PCT/EP2016/074008 WO2017060431A1 (en) 2015-10-09 2016-10-07 Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors

Publications (2)

Publication Number Publication Date
CA3000063A1 true CA3000063A1 (en) 2017-04-13
CA3000063C CA3000063C (en) 2024-09-10

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Publication number Publication date
USRE50594E1 (en) 2025-09-23
EA201890888A1 (ru) 2018-10-31
PT3359542T (pt) 2021-05-25
IL258073B (en) 2021-05-31
US10882866B1 (en) 2021-01-05
CL2018000666A1 (es) 2018-08-10
CN119569741A (zh) 2025-03-07
US10717742B2 (en) 2020-07-21
SA518391307B1 (ar) 2021-11-25
CO2018003565A2 (es) 2018-07-10
DK3359542T3 (da) 2021-05-31
SI3359542T1 (sl) 2021-08-31
JP2018533558A (ja) 2018-11-15
BR112018007155A2 (pt) 2018-11-06
US20170174695A1 (en) 2017-06-22
PL3359542T3 (pl) 2021-09-20
KR20240158360A (ko) 2024-11-04
CY1124284T1 (el) 2022-07-22
CN108137590A (zh) 2018-06-08
MX2018004207A (es) 2018-07-06
US10144739B2 (en) 2018-12-04
HK1252365A1 (en) 2019-05-24
MA50065B1 (fr) 2021-06-30
UA123905C2 (uk) 2021-06-23
NZ740312A (en) 2024-11-29
TWI737635B (zh) 2021-09-01
LT3359542T (lt) 2021-05-25
CN108137590B (zh) 2021-04-09
RS61936B1 (sr) 2021-07-30
AU2016333721A1 (en) 2018-03-22
AR106314A1 (es) 2018-01-03
EA036013B1 (ru) 2020-09-14
CN119569740A (zh) 2025-03-07
KR102722493B1 (ko) 2024-10-29
WO2017060431A1 (en) 2017-04-13
JP6602470B2 (ja) 2019-11-06
PH12018500763A1 (en) 2018-10-29
ES2873895T3 (es) 2021-11-04
US20180273541A1 (en) 2018-09-27
HRP20210960T1 (hr) 2021-09-03
MA50065A (fr) 2018-08-15
EP3359542B1 (en) 2021-03-17
HUE054985T2 (hu) 2021-11-29
IL258073A (en) 2018-05-31
PE20181205A1 (es) 2018-07-23
CN113214270A (zh) 2021-08-06
MY199688A (en) 2023-11-17
CN119569739A (zh) 2025-03-07
AU2016333721B2 (en) 2020-07-16
EP3359542A1 (en) 2018-08-15
BR112018007155B1 (pt) 2022-12-13
MX377009B (es) 2025-03-07
TW201722961A (zh) 2017-07-01
KR20180058832A (ko) 2018-06-01

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